This article first examines astrologers’ protestations at growing religious hostility in the 1490s and the involvement of Ficino, Pico and Savonarola in Florence. It then charts the reactions to Pico’s Disputationes both in the anti-astrological camp’s enthusiastic endorsement, and especially in the riposte of professional astrologers across Europe, whose piece-meal replies, intensified by the approaching conjunction of 1524, include a call for internal reform through a rejection of Arabic methods. Pico’s technical and empirical secondary arguments emerge as more effective than the physical and moral primary ones and reveal his singular understanding of practitioners’ mentality.